Polyunsaturated Fatty Acids in Pathological Retinal Angiogenesis
Undurti N. Das.
Diabetic retinopathy and age-related macular degeneration (AMD) are due to neovascularization as a result of increased production of growth hormone, insulin-like growth factor (IGF), basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-ß), hepatocyte growth factor, placental growth factor, tumor necrosis factor-α (TNF- α) and vascular endothelial growth factor (VEGF) in response to hypoxia and ischemia of the inner retinal layers. Beneficial effects of recombinant humanized anti-VEGF antibody and demonstration of enhanced levels of VEGF in the plasma and vitreal fluid in diabetic retinopathy and AMD suggests that VEGF plays a central role in pathological retinal angiogenesis. Retinopathy of prematurity initiated by hyperoxia-induced obliteration of newly formed blood vessels in the retina as a consequence of hyperoxia-induced shut-off of VEGF production by neuroglial cells leads to selective apoptosis of endothelial cells. This premature apoptosis of endothelial cells leads to hypoxia of the developing retina that, in turn, leads to the production of abnormally high levels of VEGF and hence, anti-VEGF therapy is useful in the treatment of retinopathy of prematurity. Thus, AMD, diabetic retinopathy, and retinopathy of prematurity are all characterized by high levels of VEGF and neovascularization. Recent studies revealed that increased consumption of ω-3 polyunsaturated fatty acids (PUFAs) prevent or arrest the progress of retinal neovascularization. ω-and ω-6 PUFAs and their products lipoxins, resolvins and protectins have anti-inflammatory actions, suppress VEGF and tumor necrosis factor-α (TNF-α) production, and inhibit endothelial cell proliferation that may account for their beneficial effects in pathological retinal angiogenesis. These results emphasize the role of lipids in diabetic retinopathy, AMD and retinopathy seen in premature infants.
Keywords: Angiogenesis, retinopathy, diabetes mellitus, age-related macular degeneration, inflammation, endothelial cells, vascular endothelial growth factor
Rights & PermissionsPrintExport